Clinical Diagnostic Potential and Characterization of Distinctly Hypermutated Antibodies in Multiple Sclerosis Patients
| dc.contributor.advisor | Cowell, Lindsay G. | en |
| dc.contributor.committeeMember | Monson, Nancy L. | en |
| dc.contributor.committeeMember | Wakeland, Edward K. | en |
| dc.contributor.committeeMember | Patrie, Steven M. | en |
| dc.contributor.committeeMember | Ward, E. Sally | en |
| dc.creator | Rounds, William Harold Alexander | en |
| dc.date.accessioned | 2018-08-24T20:40:46Z | |
| dc.date.available | 2018-08-24T20:40:46Z | |
| dc.date.created | 2016-08 | |
| dc.date.issued | 2016-08-12 | |
| dc.date.submitted | August 2016 | |
| dc.date.updated | 2018-08-24T20:32:23Z | |
| dc.description.abstract | Multiple sclerosis (MS) diagnosis primarily revolves around the use of brain lesion detection by MRI and the elimination of other possible neurological disorder diagnoses through clinical testing and history. For many patients first experiencing clinical symptoms that could be MS-related, this presents a challenge since diagnostic certainty based on clinical presentation and testing does not always reach a consensus among doctors who evaluate them. With a growing body of evidence for B cell involvement and dysregulation in MS, our group investigated and identified a potential biomarker in the cerebrospinal fluid of patients with MS based on B cell antibody sequencing. This work first identified a distinct mutation pattern in the antibody sequences of CSF-derived B cells, termed the antibody gene signature (AGS), that could be used to identify patients with MS or patients who would convert to MS subsequent to their first onset of clinically detectable symptoms. This thesis project outlines the transition from AGS testing in a laboratory setting to its use and implementation as an additional clinical diagnostic tool for MS (MSPrecise®) using next generation sequencing (NGS). One of its main goals is to thoroughly evaluate the performance of MSPrecise® using the far greater throughput which NGS allows for. Over the course of the project, NGS technology and accuracy optimization methods have advanced significantly. As our laboratory is the first to ever utilize NGS for somatic hypermutation evaluation, we focused strongly on the evaluation of challenges and features associated with NGS use for immune repertoire diversity and somatic hypermutation profiling of clinical samples. In this context, this project also highlights observations on sequence library preparation and post-sequencing data filtering that affect all immune repertoire research that uses these rapidly developing sequencing platforms. | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.oclc | 1049807575 | |
| dc.identifier.uri | https://hdl.handle.net/2152.5/5747 | |
| dc.language.iso | en | en |
| dc.subject | B-Lymphocytes | en |
| dc.subject | Genes, Immunoglobulin | en |
| dc.subject | High-Throughput Nucleotide Sequencing | en |
| dc.subject | Multiple Sclerosis | en |
| dc.subject | Sequence Analysis, DNA | en |
| dc.title | Clinical Diagnostic Potential and Characterization of Distinctly Hypermutated Antibodies in Multiple Sclerosis Patients | en |
| dc.type | Thesis | en |
| dc.type.material | text | en |
| thesis.degree.department | Graduate School of Biomedical Sciences | en |
| thesis.degree.discipline | Immunology | en |
| thesis.degree.grantor | UT Southwestern Medical Center | en |
| thesis.degree.level | Doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |